RESUMO
We describe a boy with Fisher syndrome. He presented the typical symptoms of Fisher syndrome, including external ophthalmoplegia, abnormality of convergence, and areflexia, after an episode of Campylobacter enterocolitis. Atypically, however, anti-GA1 antibody was detected in his serum, though anti-GQ1b and anti-GT1a antibodies were not. In addition, the tau protein level in his cerebrospinal fluid was elevated. Generally, Fisher syndrome is a self-limiting disease and has a good prognosis. In our patient, however, mild diplopia and areflexia persisted 6 months after their onset. Here, we report on the first Fisher syndrome patient with anti-GA1 antibody in the serum and elevated tau protein in the cerebrospinal fluid.
Assuntos
Autoanticorpos/biossíntese , Doenças Autoimunes do Sistema Nervoso/líquido cefalorraquidiano , Gangliosídeos/imunologia , Síndrome de Miller Fisher/líquido cefalorraquidiano , Proteínas tau/biossíntese , Proteínas tau/líquido cefalorraquidiano , Autoanticorpos/sangue , Doenças Autoimunes do Sistema Nervoso/imunologia , Doenças Autoimunes do Sistema Nervoso/microbiologia , Infecções por Campylobacter/líquido cefalorraquidiano , Infecções por Campylobacter/imunologia , Criança , Humanos , Masculino , Síndrome de Miller Fisher/imunologia , Síndrome de Miller Fisher/microbiologia , Regulação para Cima/imunologia , Proteínas tau/sangueRESUMO
CpG DNA has immunomodulatory effects, such as the suppression of allergic responses mediated by type II T cell help (T(H)2). Here we report that CpG, but not lipopolysaccharide (LPS), rapidly induces expression of T-bet mRNA in purified B cells. Up-regulation of T-bet by CpG is abrogated in mice deficient in Toll-like receptor 9 (TLR9) and MyD88, but remains intact in B cells deficient in STAT1 (signal transducer and activator of transcription 1). Interleukin 12 (IL-12) alone does not up-regulate T-bet mRNA, but greatly enhances CpG-induced T-bet expression. Furthermore, CpG inhibits immunoglobulin G1 (IgG1) and IgE switching induced by IL-4 and CD40 signaling in purified B cells, and this effect correlates with up-regulation of T-bet. Thus, CpG triggers anti-allergic immune responses by directly regulating T-bet expression via a signaling pathway in B cells that is dependent upon TLR9, independent of interferon-gamma (IFN-gamma)-STAT1 and synergistic with IL-12.
Assuntos
Linfócitos B/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Switching de Imunoglobulina/efeitos dos fármacos , Imunoglobulina E/biossíntese , Imunoglobulina G/biossíntese , Oligodesoxirribonucleotídeos/farmacologia , Fatores de Transcrição/genética , Animais , Linfócitos B/imunologia , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/fisiologia , Imunoglobulina G/classificação , Interferon gama/fisiologia , Interleucina-12/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/fisiologia , NF-kappa B/fisiologia , Receptores de Superfície Celular/fisiologia , Recombinação Genética , Fator de Transcrição STAT1 , Proteínas com Domínio T , Receptor Toll-Like 9 , Transativadores/metabolismo , Transcrição Gênica , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
Immunosurveillance requires the coordinated regulation of chemokines and adhesion molecules to guide immune cell migration. However, the critical molecule for governing the high trafficking capability of immune cells is not clear. Here we show that the effector molecule RAPL is indispensable in the integrin-mediated adhesion and migration of lymphocytes and dendritic cells. RAPL deficiency caused defective chemokine-triggered lymphocyte adhesion and migration to secondary lymphoid organs, resulting in atrophic lymphoid follicles and deficient marginal zone B cells, concomitant with increased immature B cells in the blood. Furthermore, splenic dendritic cells were diminished and defective in adhesion. After being activated with inflammatory stimuli, skin and splenic dendritic cells failed to migrate into either the draining lymph nodes or the white pulp of the spleen. Thus, RAPL is a crucial immune cell trafficking regulator essential for immunosurveillance.